Human breath samples typically contains 50-60 organic compounds and may contain as many as 200 or more, all in rather small abundances. Evidence is accumulating that suggests that specific metabolic conditions or disease states may result in evaluated presences of certain organic compounds on breath. However the quantification of individual compounds remains an arduous task and the complete characterization, to very low detection limits, of even the majority of compounds in any breath sample remains unknown at this time. Chemical Reaction Mass Spectrometry (CRMS) holds exceptional promise for the simultaneous identification and quantification numerous trace organics in humid environments such as breath (i.e., creating a "fingerprint of breath organics"). The work carried out for this grant will be to develop a CRMS, the requisite methodology, and the validation processes, to permit the characterization (both identification and most importantly, quantification) of many, perhaps even most, trace organics in any breath sample, or indeed, in any gaseous sample. The promise of breath analysis as a noninvasive diagnostic and monitoring method has been known for many years, but its implementation has been limited by inadequate instrumental methods; the CRMS will be substantially faster and more sensitive than previous methods employed (e.g., GC-MS). The specific aims of the proposal include: (1) Implementing a state-of-art CRMS that has very low detection limits, broad applicability, and completely documented methods, and validations. (2) Developing and documenting new reagent ions for CRMS that are as efficient as the proton transfer reagent ion H30+ but which do not suffer from the severe limitations due to the hydration of H30 + in humid environments (such as breath). The new ions targeted for development are trimethylsilyl transfer reagents such as [(CH3)3Si]0+. (3) Demonstrating the robustness of the instrumentation and methodology on multiple "standard samples" in order to support arguments for the advancement to testing of human breath.